Researchers at the Massachusetts Institute of Technology have perfected a delivery technique that appears to make gene silencing therapy ready for clinical trials. This is big news for a lot of genetic conditions possibly including autoimmune disease.
If malfunctioning immune genes could be ‘silenced’ for a time then our out of control immune systems might be able to be brought under control.
Gene silencing techniques have been available for last eight or ten years, but were not practical due to delivery problems. MIT researchers seem to have solved the problem by wrapping the gene silencing materials (siRNA) in a special coating of a fat like molecule that is readily absorbed by cells. Once inside the cell the silencing RNA is released to turn off the defective genes.
Sounds promising to me, but I have been disappointed before. Can you say Prochymal from Osiris?
I think this particular technique is a much more likely to work than not. MIT researchers have reputations to protect. Let’s hope they get funding for the quick development of effective treatments and cures for so many diseases, now untreatable.
Personal note: I am still fighting a resistant bacterial infection of my right nostril. At present I seem to be losing both sides of the battle. My immune system itches more and more with the top of the line restricted antibiotic (Zyvox) each time I take it and sadly the bacteria seems to be less and less affected by the Zyvox. Initially it died nicely. Not as good as the sulfa drug killed it but very nicely.
This morning’s dose of Zyvox barely affected the bacteria. I felt the rush of Zyvox hit me about an hour and half after ingesting the pill at 7am. Within minutes I felt a few of the scabs losing up and coming off as the bacteria were killed. But most scabs and sores were unaffected. Pain in the bones around my eye and cheekbones are increasing.
I am taking the maximum dose of Zyvox so the doctor also prescribed mupirocin spray and ointment in combination with the Zyvox. Sadly mupirocin also has lost its power over these bacteria. Originally it seemed that it alone would kill them. Now they act like it does not bother them at all to be drenched in the stuff. yet my immune system reacts in violent itching which I try to control with pre treatment of H1 and H2 antihistamine blockers (Zyrtec, Chlortrimeton, and Zantac)
I see the ear nose and throat guy tomorrow. He could try IV antibiotics, but it is unlikely that my immune system would tolerate them for as long a time as I would need to kill the bacteria.
Hypersensitivity reactions are life threatening and often treated as a joke on TV with someone swollen up or covered with hives being used for a punchline to a gag. However, when there is a systemic (whole body) malfunction of the immune system, like swelling (angioedema) or hives, that is not a joke. It is very often a medical emergency.
The odds were stacked against me when I acquired the infection and have gotten worse as either I reacted to medications like sulfa or the bacteria fought off the medication like Avelox. This country and the world desperately need new and completely novel antibiotics.
All Big Pharma ever seems to give us are the same old antibiotics just with new chemical side groups and other minor tweeks that allow the companies to market as a “new” antibiotic, a very similar one to what we already had.
Unless something positive happens quickly, things look a bit bleak for me. But hopefully the new gene silencing delivery system from MIT will make a difference for cures for you and for my son, Paul. Sure wish there were a gene silencing technique for hypersensitivity genes right about now.
New RNA interference technique can silence up to 5 genes
December 28, 2009
Researchers at MIT and Alnylam Pharmaceuticals report this week that they have successfully used RNA interference to turn off multiple genes in the livers of mice, an advance that could lead to new treatments for diseases of the liver and other organs.
Since the 1998 discovery of RNA interference — the naturally occurring phenomenon in which the flow of genetic information from a cell's nucleus to the protein-building machinery of the cell is disrupted — scientists have been pursuing the tantalizing ability to shut off any gene in the body. Specifically, they have been trying to silence malfunctioning genes that cause diseases such as cancer.
The new delivery method, described in the Proceedings of the National Academy of Sciences, is orders of magnitude more effective than previous methods, says Daniel Anderson, senior author of the paper and a biomedical engineer at the David H. Koch Institute for Integrative Cancer Research at MIT.
"This greatly improved efficacy allows us to dramatically decrease the dose levels, and also opens the door to formulations that can simultaneously inhibit multiple genes or pathways," says Anderson.
The key to success with RNA interference is finding a safe and effective way to deliver the short strands of RNA that can bind with and destroy messenger RNA, which carries instructions from the nucleus.
Anderson and his colleagues believe the best way to do that is to wrap short interfering RNA (siRNA) in a layer of fat-like molecules called lipidoids, which can cross cells' fatty outer membrane. Using one such lipidoid, the researchers were able to successfully deliver five snippets of RNA at once, and Anderson believes the lipidoids have the potential to deliver as many as 20.
How they did it: The team at MIT, along with Alnylam researchers, have developed methods to rapidly produce, assemble and screen a variety of different lipidoids, allowing them to pick out the most effective ones.
In a previous study, the researchers created more than 1,000 lipidoids. For their latest study, they picked out one of the most effective and used a novel chemical reaction to create a new library of 126 similar molecules. The team focused on one that appeared the most promising, dubbed C12-200.
Using C12-200, the researchers achieved effective gene silencing with a dose of less than 0.01 milligrams of siRNA per kilogram of solution, and 0.01 milligrams per kilogram in non-human primates. If the same dosing were translated to humans, a potential therapy would only require an injection of less than 1 milliliter to specifically inhibit a gene, compared with previous formulations that would have required hundreds of milliliters, says Anderson.
Other authors from MIT include Kevin T. Love, Kerry P. Mahon, Christopher G. Levins, Kathryn A. Whitehead and Institute Professor Robert Langer.
Next steps: The MIT/Alnylam team hopes to start clinical trials within the next couple of years, after figuring out optimal doses and scaling up the manufacturing capability so they can produce large amounts of the siRNA-lipidoid complex.
More information: "Lipid-Like Materials for Low Dose, in vivo Gene Silencing," Kevin T. Love, Kerry P. Mahon et al. Proceedings of the National Academy of Sciences, week of Dec. 28, 2009.
Provided by Massachusetts Institute of Technology